Salts of the extractive product from the hypophysis gland.



. residing at Hochst-on-the-Main, have invented certain new and useful Tmj diluted entire area an on.

FRANZ FLAECHER AND BAPTIST REUTER, OF Hi'jCHST-ON-THE-MAIN, GERMANY, ASSIGNORS T0 FARCBWERKE VORM'. MEISTER LUCIUS & BR'U'NIN G,

or nocnsr- ON-THE-MAIN', GERMANY, a CORPORATION or enema Y SALTS OF THE EXTRACTIVE PRODUCT FROM THE HYPOPHYSIS GLAND.

To all whom it may concern:

chemist, citizens of the Empire of Germany;

provements in Salts of the Extractive Prod-i not from the Hypophysis Gland, the following is a specification In U. S. patentapplication Ser. No. 722245 filed 25th Sept. 1912, is described a new product possessing the blood-pressureraising, hemostatic, astringent and laborpains-promoting properties of the physiologically active element of the lnfundibular portion of the hypophysis gland, in a pure,

concentrated and stable form. This product Y is a base, obtained as conglomerations of small yellowish-white prisms, difficultly solable in alcohol, ether, ethyl-acetate and acetone, soluble in alkalis and acids, prec pitated by the usual alkaloid reagents,

giving a red coloration with diazotized sulfanilic acid in a solution alkaline with soda, and giving the biuret-reaction The base is readily soluble in water, but it then shows an alkaline reaction which is of some disadvantage in its administration.

In order to obtain this basic product we proceed as follows:

pletely freeing the filtrate and evaporating it. The concentrated extract thus obtained is acidified with slightly whereupon an aqueous causes precipitation. precipitate, which consists of the phosphotungstic compound of the active base, is well washed with acidified with sulfuric acid, and mixed and stirred with water so as to form a thin magma, and finally barium hydrate is added until there is a distinct alkaline reaction. The so-formed phosphotungstate of barium is filtered off, the filtrate is freed from the dissolved barium by addition of diluted sulfuric acid, taking care to avoid an excess of this acid, and is then evaporated in cacao ,to crystallization Be it known that we, FRANZ FLAEOHER,

Ph. D., chemist, and BAPTIST REUTER, Ph. D.,"fetc., washed with alcohol and dried in German of which 7 poses at 160-161 C.

or the base may he means of precipitated by alcohol, acetone.

ocwuo. A

Now We have tamable from the found that the salts obsaid base do not show the aforementioned disadvantage. These salts are well-crystallized, in water and ave t action as the base.

hus We prepare of the said base by dissolving it in a small quantity of water and adding to this solution diluted sulfuric acid until there is a slightly acid reaction. The concentrated solution is then evaporated in a vacuum to the point of crystallization. The sulfate of the active substance of the hypophysis. thus obtained, forms a slightly yellowish. stable, crystalline powder, which decomand readily dissolves in water, with slightly acid reaction. and is difficultly soluble in alcohol, ether. ethylacetate and acetone; it shows the diazo reaction referred to by Pauly see Zw'fs'c/uv'ff fair Pitg sz'ologz'sche Ohemiw, vol. 42, page 5 giving ared coloration when treated diazotized sulfanilic acid in a solution alkaline with soda. It also shows the biuretreaction and is precipitated by the usual alkaloid reagents. lVhen subjected to Erdmanns test, the salt first becomes colorless, then yellow; when subjected to Friihdcs test, first colorless, then yellow, afterward green and again yellow; in presence of vanadiumsulfuric acid, first colorless, then pure yellow. sulfuric acid there may also be used other acids, for instance hydrochloric acid, nitric acid, boric acid, succinic acid, oxalic acid, citric acid, tartaric acid, acetic acid, benzoic acid, salicylic acid, etc,

stable, readily soluble e same physiological used, are obtained. lutions in water of the before-mentioned salts are of great value for therapeutical purposes. The solution obtained by dissolving such a salt-composition in water, for example the sulfate, has a slightly acid reaction, and possesses the blood-pressure raising, hemostatic, astringent and laborpains promoting properties of the principles of the hypophysis gland it is precipitated for instance the sulfate by the usual alkaloid reagents, giving a red coloration when treated with diazotized sulfanilic acid in a solution alkaline with sodium carbonate, and showing the biuretreaction. When the solution is cautiously evaporated in raw-o, a salt, for example the sulfate, remains, which forms a yellowishwhite, stable, crystalline powder and decomposes when heated to 160161 C., and which is readily soluble in water with slightly acid reaction, also soluble in acids and alkalis,

soluble in alcohol, ether, ethylacetate and acetone. If it is subjected to Erdmanns test, it first becomes colorless and afterward yellow; if subjected to Froehdes test, first colorless then pure yellow, and if treated with vanadium-sulfuric acid, first colorless and afterward pure yellow.

Having now described our invention, what we claim is:

1. As new compositions 5f matter, crystalline salts of a basic substance, such as can be obtained from the infundibular lobe of the pituitary gland by the herein described process which comprises extracting the lobe with slightly acidulated water and precipitating the basic substance from said extract with phosphotungstic acid, said salts having hemostatic, astringent, blood-pressure raising and labor-pains promoting properties, being soluble in water with slightly acid reaction, diflicultly soluble in alcohol, ether, acetone and ethyl acetate, readily soluble in acids and alkalis, being precipitated by the usual alkaloid reagents, giving a red coloration when treated with diazotized sulfanilic acid in a solution alkaline with soda, and giving the biuret-reaction.

2. The substance consisting of a crystalline sulfate of a basic substance, such as can be obtained from the infundibular lobe of the pituitary gland by the herein described process which comprises extracting the lobe with slightly acidulated tating the basic substance from said extract with phosphotungstic acid, said salt being a faint yellowish-white, stable, crystalline powder, decomposing at 160-161 C., readily soluble in water with slightly acid reaction, diflicultly soluble in alcohol, ether, acetone, ethylacetate, also alkaloid reagents, giving a red coloration when treated with diazotized sulfanilic acidin a solution alkaline with soda, showing the biuret-reaction, and possessing the properties of the hemostatic, astringent, blood-pressure raising and labor-pains promoting prinwater and preclpisoluble in acids and alkalis, being precipitated by the usual cipl'e of the infundibular portion of the hypophysis gland.

3. Water solutions of salts of a basic substance, (such as can be obtained from theinfundibular lobe of the pituitary gland by the hereindescribed process which comprises extracting the lobe with slightly acidulated water and precipitating the basic substance from said extract with phosphotungstic acid), said solutions having a slightly acid reaction and being characterized by their hemostatic, astringent, blood-pressure raising and labor-pains promoting action, said solutions being precipitated by the usual alkaloid reagents, assuming a red coloration when treated with diazotized sulfanilic acid in a solution alkaline with sodium carbonate, giving the biuret-reaction, and yielding when cautiously evaporated in ammo, crystalline bodies which are organic salt-combinations forming yellowish-white, stable, crystalline powders, decomposing when heated, readily soluble in water with slightly acid reaction, soluble in acids and alkalis, and difiicultly soluble in alcohol, ether, acetone and ethyl-acetate.

4. A water solution of the sulfate of a basic substance, (such as can be obtained from the 'infundibular lobe of the pituitary gland by the hereindescribed process which comprises extracting the lobe withslightly acidulated water and precipitating the basic substance from said extract with phosphotungstic acid), said solutions having a slightly acid reaction and being characterized by its hemostatic, astringent, bloodpressure raising and labor-pains promoting action, said solution being precipitated by the usual alkaloid reagents, assuming a red coloration when treated with diazotized sulfanilic acid in a solution alkaline with sodium carbonate, giving the biuret-reaction, and yielding when cautiously evaporated in 'vacuo a crystalline body which is an organic salt-combination, which combination forms a yellowish-white, stable, crystalline powder, decomposing when heated to 160-161 (3., readily soluble in water with slightly acid reaction, soluble in acids and alkalis, and diiiicultly soluble in alcohol, ether, acetone and ethyl-acetate.

In testimony whereof, we aflix our signatures in presence of two witnesses.

FRANZ FLAEC-HER. BAPTIST REUTER.

Witnesses JEAN GRUND, CARL GRUND. 

